rs1138484

Variant names:

• chr2-85861188-T-A
• rs1138484
• NM_003896.4:c.311A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-85861188-T-A
• chr2-85861188-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001354223.2(ST3GAL5):​c.-251A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000969 in 1,445,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: ST3GAL5 NM_001354223.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.10
• Publications: 27 publications found

Genes affected

ST3GAL5 (HGNC:10872): (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ST3GAL5 Gene-Disease associations (from GenCC):

• GM3 synthase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08435607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354223.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	NM_003896.4	MANE Select	c.311A>T	p.His104Leu	missense	Exon 3 of 7	NP_003887.3
	ST3GAL5	NM_001354223.2		c.-251A>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 9	NP_001341152.1
	ST3GAL5	NM_001354224.2		c.-314A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	NP_001341153.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.311A>T	p.His104Leu	missense	Exon 3 of 7	ENSP00000491316.1	Q9UNP4-1
	ST3GAL5	ENST00000393808.8	TSL:1	c.242A>T	p.His81Leu	missense	Exon 3 of 7	ENSP00000377397.3	Q9UNP4-3
	ST3GAL5	ENST00000393805.6	TSL:1	c.227A>T	p.His76Leu	missense	Exon 3 of 7	ENSP00000377394.1	Q9UNP4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000969 AC: 14 AN: 1445492 Hom.: 0 Cov.: 29 AF XY: 0.0000167 AC XY: 12 AN XY: 720300

African (AFR) AF: 0.000211 AC: 7 AN: 33202

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53292

Middle Eastern (MID) AF: 0.000187 AC: 1 AN: 5346

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097634

Other (OTH) AF: 0.0000501 AC: 3 AN: 59868

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 13073

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	GM3 synthase deficiency (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.12
Sift	Benign	0.067	T
Sift4G	Benign	0.67	T
Polyphen		0.026	B
Vest4		0.25
MutPred		0.39		Loss of disorder (P = 0.0183)
MVP		0.38
MPC		0.39
ClinPred		0.20	T
GERP RS		5.0
Varity_R		0.077
gMVP		0.71
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1138484; hg19: chr2-86088311;